1. Field of the Invention
The present disclosure relates to the combination of known biologically active compounds for the treatment of acid-related gastrointestinal disorders. The compounds used in the combination according to the present disclosure are known gastric acid secretion inhibitors in combination with ALA or related compounds. ALA is not known as a treatment for acid related gastrointestinal disorders, nor is it anywhere suggested that ALA would be useful for the treatment of acid-related gastrointestinal disorders, or useful for the enhancement of current treatments for acid-related gastrointestinal disorders. Unexpectedly, ALA, when combined as described in the present disclosure with certain common compounds used in the treatment of acid-related gastrointestinal disorders, has a synergistic effect in improving symptoms.
Acid-related gastrointestinal disorders include gastroesophageal reflux disease (GERD), heartburn, and gastrointestinal ulcers. GERD is a digestive disorder that affects the lower esophageal sphincter (LES), the ring of muscle between the esophagus and stomach. Doctors believe that GERD may be caused by hiatal hernia. Frequently, heartburn can be relieved through diet and lifestyle changes; however, some people may require medication or surgery.
Gastroesophageal refers to the stomach and esophagus. Reflux means to flow back or return. Therefore, gastroesophageal reflux is the return of the stomach's contents back up into the esophagus. In normal digestion, the lower esophageal sphincter (LES) opens to allow food to pass into the stomach and closes to prevent food and acidic stomach juices from flowing back into the esophagus. Gastroesophageal reflux occurs when the LES is weak or relaxes inappropriately; allowing the contents of the stomach to flow up into the esophagus. The refluxed liquid can inflame and damage the lining of the esophagus. This liquid may also contain bile that has backed-up into the stomach from the duodenum. Acid is believed to be the most harmful component of refluxed liquid. Pepsin and bile also may injure the esophagus, but their role in esophageal inflammation and damage is unclear. The severity of GERD depends on LES dysfunction, the type and amount of refluxed liquid and the neutralizing effect of saliva.
GERD is a chronic condition; once it begins, it usually is life-long. Injury to the lining resulting from GERD is also typically chronic. Moreover, after the esophagus has healed with treatment and treatment is stopped, the injury will return in most patients within a few months. Once treatment for GERD is begun, it will typically need to be continued indefinitely.
Heartburn, also called acid indigestion, is the most common symptom of GERD and usually feels like a burning chest pain beginning behind the breastbone and moving upward to the neck and throat. More than 60 million American adults experience heartburn at least once a month, and more than 15 million adults suffer daily from heartburn. Heartburn affects men, women and children alike.
The body has natural defenses against the harmful effects of acid reflux. For example, most reflux occurs during waking hours when individuals are upright. In the upright position, gravity causes the refluxed liquid to flow back down into the stomach. Further, during waking hours, individuals repeatedly swallow, regardless of reflux. Each swallow returns refluxed liquid to the stomach. In addition, saliva contains bicarbonate. With each swallow, bicarbonate-containing saliva travels down the esophagus. The bicarbonate neutralizes normal amounts of acid in the esophagus. During sleep, gravity has no in effect, swallowing stops, and the secretion of saliva is reduced. Therefore, reflux that occurs at night is more likely to result in acid remaining in the esophagus longer and causing greater damage to the esophagus.
Pharmacological medicine has established that gastroesophageal reflux disease and gastrointestinal ulcers are induced by unbalance between aggressive factors, e.g. hydrochloric acid, pepsin, and defensive factors, e.g. mucosal blood flow and mucus secretions. Therefore, it is desirous to have available some synthetic and/or natural substance that exhibits pharmacological activity of both an action of inhibiting gastric acid secretion and an action of enhancing protection of the gastric mucosa.
2. Summary of the Related Art
Standard treatment for acid-related gastrointestinal disorders involves the use of proton pump inhibitors and histamine H2 acid receptor antagonists. Both classes of drugs work by suppressing gastric acid secretion.
Proton pump inhibitors (PPI's) are compounds that suppress gastric acid secretion by the specific inhibition of the H+/K+−-ATPase enzyme system (proton pump) at the secretory surface of the gastric parietal cell. Practically, over the counter (OTC) PPI's have become the mainstay in the management of gastroesophageal reflux disease (gerd) and gastric acid secretions. Common OTC drug compounds in the class of proton pump inhibitors are Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole, Esomeprazole, and Zegerid. These PPI's belong to a chemical class found to be useful as gastric acid secretion inhibitors. An early patent representative of PPI's is U.S. Pat. No. 4,255,43, which teaches the use of 2-(2-benzimidazolyl)-pyridines as a method for inhibiting gastric acid secretion.
Histamine H2-acid receptor antagonists were developed as drugs for the treatment of acid-peptic disease, including duodenal and gastric ulcers, gastroesophageal reflux disease and common heartburn. Histamine interaction with H2 receptors in the parietal cells of the gastric mucosa results in the secretion of gastric acid. Histamine H2-acid receptor antagonists compete effectively with histamine to block gastric secretions. Common histamine H2-acid receptor antagonist's drug compounds include Ranitidine HCL, Cimetidine, Famotidine, and Nizatidine. An early patent representative of PPI's is U.S. Pat. No. 4,128,658, which teaches the use of aminoalkyl furan derivatives or physiological salts of N-oxide or compounds thereof, to inhibit histamine H2-acid receptor antagonist's activity.
While both PPI's and histamine H2 acid receptors have been generally successful for treating acid-related gastrointestinal disorders, for many they have not been fully successful. New surveillance data on GERD patients indicates that almost half of GERD persons don't get complete relief from GERD symptoms even while taking proton pump inhibitors (PPI's), the strongest medication currently offered for gastroesophageal reflux or heartburn. Thus, it is readily apparent there exists a need for faster acting and more effective treatment regimens to better manage GERD and severe heartburn. Therefore, a means of enhancing the effects of known drugs is desired.